In a recent randomized and blinded multi-institutional clinical study, we found that corticosteroids administered twice (12 hours and 2 hours prior to contrast material challenge conferred significant protection against intravenous ionic contrast material (C.M.) systemic reactions. No significant adverse effects could be attributed to the steroids alone. In comparing these results to those reported in a large (non-blinded and non-randomized) study of systemic reactions following the injection of nonionic C.M., we noted that the incidence of "reaction necessitating therapy" did not differ significantly in the two studies. This suggested that routine pretreatment with corticosteroids preceding the intravenous injection of ionic media might be effectively substituted for the much more expenseve utilization of nonionic media (without pretreatment). No controlled randomized study of I.V. injections can be made. Early studies in this laboratory suggested that the mechanism of steroid protection against C.M. reactions might include a down- regulation of contact system activation products. We propose to further examine this thesis by utilizing targeted blood specimens from participants in the proposed clinical study. These will be assayed for various factors that bear on the dynamics of contact system activity in reactors and controls identified in the course of the study. Specifically, we will assay for concentrations of alpha2-macroglobulin, C1-esterase inhibitor, alpha2-macroglobulin- kallikrein, angiotensin-converting enzyme, and circulating negative soluble "surfaces". We will also examine the rate of prekallikrein-to-kallikrein transformation engendered by exposure of diluted plasma samples to an exogenous contact system activator. The appropriate correlation of these parameters with steroid treatment, in reactors or non-reactors, should supply us with additional valuable insights regarding the mechanisms of corticosteroid protection and the pathogenesis of C.M. reactions.